The Treatment of Pancreatitis.

Published reports suggest a considerable geographical variation in the pathogenesis of acute pancreatitis (Table 1). This may account for the contradictory findings regarding the effectiveness of the commonly used therapeutic agents Propantheline Bromide (Pro-Banthine), Aprotinin and Glucagon. In most studies, the majority of cases have been associated with biliary disease, an undetermined proportion having a stone in the ampulla of vater obstructing the common opening of the bile and pancreatic ducts so enabling bile to reflux into the


INTRODUCTION
Published reports suggest a considerable geographical variation in the pathogenesis of acute pancreatitis (Table 1). This may account for the contradictory findings regarding the effectiveness of the commonly used therapeutic agents Propantheline Bromide (Pro-Banthine), Aprotinin and Glucagon.
In most studies, the majority of cases have been associated with biliary disease, an undetermined proportion having a stone in the ampulla of vater obstructing the common opening of the bile and pancreatic ducts so enabling bile to reflux into the pancreas (Opies syndrome). The study here reported was prompted by our own experience of the remarkable effectiveness of Glucagon not only in reducing mortality and morbidity of our patients, but also in controlling pain where it has proved as effective as Pethidine in the acute stages of the disease.
Our study is retrospective but allocation to treatment groups was random and treatment groups were statistically comparable in respect of age, sex and serum amylase levels (Tables 2 and 3).  (1) History and clinical signs comparable with acute pancreatitis.
(2) Serum amylase raised to more than twice the maximum normal limit of 300 u/litre Int. Units.
Allocation to treatment groups was random since treatment depended on to which of three surgical services on emergency rota the patients were admitted. On one surgical service, the policy was to   give Glucagon 1 mg six hourly. On the second service, Propantheline 15mg was given six hourly and on the third, the policy changed from Propantheline to Glucagon during the period of study. In all cases, gastric aspiration and i.v. fluids were given during the acute stage, together with Ampicillin 250 mg to 500mg six hourly to prevent infection.
Excluded from the study were a small number of patients who had developed the disease after biliary surgery and a few who had inadvertently received both Glucagon and Propantheline and a few whose records were inadequate. Statistical study in respect of (sex, age and) severity of disease as judged by amylase levels confirmed the comparability of the two groups (Tables 2 and 3). Results of treatment were judged by (a) mortality, (b) length of stay in hospital, (c) rate of fall of serum amylase, (d) amounts of Pethidine required to control pain.

RESULTS
In the Glucagon group, three of the seventy patients (4%) died, none from pancreatitis, whereas in the Propantheline group, nine of the ninety died (10%), 34 five of them from uncontrolled pancreatitis. Table 4 shows the cause of deaths in the two groups. In addition, one patient in the Propantheline group developed a pseduo-pancreatic cyst. The mean length of hosptial stay was ten days with Glucagon and fourteen days with Propantheline. The more rapid recovery with Glucagon was confirmed statistically by a more rapid fall in serum amylase levels.
Control of pain in both groups was with Pethidine because unlike other opiates, it is thought not to cause spasm of the sphincter of Oddi. An average of only three doses of Pethidine were given to the Glucagon patients, whereas in the Propantheline group, it was required four hourly at least for 48 hours and sometimes as long as ten days. In the latter part of the study, it was realized that Glucagon was usually as effective as Pethidine in controlling pain and in some cases, no Pethidine at all was given. If pain recurred, an extra dose of Glucagon usually gave relief.

DISCUSSION
In the treatment of acute pancreatitis, all are agreed on the paramount importance of maintaining fluid and electrolyte balance, but opinions vary in relation to other treatment. On the one hand, some advise no further therapy whereas others, particularly in stone cases, operate to drain the area or to explore the ducts. Protagonists of the latter policy are encouraged by the frequent finding of stones impacted in the ampulla of vater (Opies syndrome). Acosta et al5 discovered calculi in 33 out of his 45 causes so explored. Majority opinion favours a conservative approach in the acute disease using anti-cholinergic drugs (Propantheline), anti-trypsin (Aprotinin) or Glucagon. The relative value of these treatments is not decided and our own experience is at variance with that of the M.R.C. Multicentre study2 in that we found Glucagon to be effective not only in reducing mortality and morbidity but also almost as effective as Pethidine in relieving pain. Our clinical material was not, however, statistically comparable with that of the M. R. C. trial which included a greater proportion of alcohol related and idiopathic cases. Aprotinin should theoretically be helpful and is reported to be beneficial providing treatment is started within 24 hours. Few of our cases have presented within this time and in the past perhaps, because of this, we found response to this treatment to be much less dramatic than that subsequently seen with Glucagon. Propantheline, likewise, should be effective since experimentally pancreatic flow and enzyme secretion are reduced. Unfortunately in the dosage required, the complications of Ileus, urinary retention, tachycardia and visual disturbances are distressing and even dangerous in the ill patient. studies, and the fact that almost all our cases were associated with biliary disease, rather than alcohol.

SUMMARY
In an area where acute pancreatitis is common and usually associated with biliary disease, a retrospective study of statistically comparable groups of patients has clearly shown the therapeutic superiority of Glucagon over Propantheline. Recovery was more rapid and amylase levels fell more quickly. Mortality with Glucagon treatment was 3/70 (4%) and with Propantheline 9/90 (10%). Length of stay in hospital was shorter and analgesic requirements greatly reduced.